By Brenda L. Mooney
BUFFALO, NY – Blast injury might be a factor in the development of post-traumatic stress disorder (PTSD) by servicemembers in combat, even if mild traumatic brain injury (TBI) is never diagnosed.
Research published recently in The Journal of Head Trauma Rehabilitation suggests that PTSD level appears to be related to not only the severity of combat stress but also the underlying structural brain changes that can be seen through diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI).1
“These brain changes may be due to neurochemical alterations induced by chronic stress or, more likely, by subclinical brain injury from blast exposure,” wrote researchers from University of Rochester, NY, School of Medicine, VA Western New York Healthcare System in Buffalo, NY, and Canandaigua, NY, VAMC. “A clinical diagnosis of mild TBI does not seem to play a role, either because it is inaccurately reported or because it correlates poorly with underlying brain injury.”
The authors, led by Jeffrey J. Bazarian, MD, MPH, of the University of Rochester Department of Emergency Medicine, call for greater efforts to screen troops for blast injury, especially because it might play a role “in the genesis of PTSD in a combat environment.”
“While screening thousands of service members with MRI or DTI may not be feasible, our results highlight the pressing need to develop practical mild TBI biomarkers (blood, electroencephalogram, etc.) that correlate with underlying brain injury,” they suggested.
The researchers said they expected PTSD severity to be strongly linked to exposure to traumatic combat events, but they also found that it was associated with high 1st percentile of mean diffusivity (MD) on DTI and white matter (WM) lesions on MRI.
“Although the association of PTSD with combat intensity has been reported by prior investigators, we are the first to find an association between DTI abnormalities and PTSD acquired in a combat setting,” the authors wrote.
For the study, researchers performed a nested cohort study of 52 Iraq and Afghanistan veterans who served in combat areas between 2001 and 2008. They were drawn from a parent cohort of 500 recent veterans from Veterans Integrated Service Network (VISN) 2, recruited between August 2008 and January 2010 as part of a study of cognitive, affective and behavioral correlates of veterans with and without TBI, which was funded by VA Health Services Research and Development.
Subjects, enrolled through several VA medical centers in upstate New York, were selected based on willingness to travel to the DTI site, to undergo DTI scanning, and because they lacked any contraindications to scanning, such as retained metallic foreign bodies or claustrophobia. DTI was not available at any VISN 2 facilities at the time.
Participants were evaluated for PTSD severity, mild TBI diagnosis and severity of exposure to traumatic events.
After imaging, PTSD severity was associated with severity of exposure to combat events, age, time since last tour, abnormal T1/T2-weighted MRI, and 1st percentile of MD on DTI. PTSD severity was an average of 13.3 points higher in the five subjects with abnormal T1/T2-weighted MRI than the 46 subjects with normal scans, according to the study.
PTSD severity was associated with higher 1st percentile values of mean diffusivity on DTI (regression coefficient [r] = 4.2, P = .039), abnormal MRI (r = 13.3, P = .046), and the severity of exposure to combat events (r = 5.4, P = .007). On the other hand, mild TBI was not significantly associated with PTSD severity.
Blast exposure, meanwhile, was associated with lower 1st percentile values of fractional anisotropy on DTI (odds ratio [OR] = 0.38 per SD; 95% confidence interval [CI], 0.15-0.92), normal MRI (OR = 0.00, 95% likelihood ratio test CI, 0.00-0.09), and the severity of exposure to traumatic events (OR = 3.64 per SD; 95% CI, 1.40-9.43).
The authors offered several explanations for the association between PTSD and abnormal DTI, including the possibility that DTI changes were caused by combat stress, which they suggested as unlikely.
“An alternative explanation is that physical forces to the brain encountered during the course of combat operations—such as blast exposure or frank mild TBI—lead to brain injury that increases the vulnerability to PTSD,” they write, pointing to some rodent studies that support that supposition.
They note that it was less clear why PTSD would be associated with WM lesions on MRI, although previous studies have had similar results. “Regardless of etiology,” the report states, “these lesions may be useful in identifying those at increased risk of PTSD.”
One issue, according to the researchers, is that, while some mild TBI patients have no post-concussive symptoms, no demonstrable cognitive deficits and normal neuroimaging, other patients who do not meet the clinical definition of mild TBI after a blow to the head have objective evidence of brain injury.
“This poor correlation to brain injury likely confounds attempts to understand the relation between mild TBI and PTSD and underscores the urgent need to develop objective aids to the diagnosis through the use of biomarkers such as neuroimaging, electroencephalography and serum protein tests,” they suggest.
The authors add that some of those questions can be resolved by better understanding how blast exposure can induce subclinical brain injury.
The article was part of a special issue of The Journal of Head Trauma Rehabilitation, official journal of the Brain Injury Association of America, a publication devoted to new research in military TBI.
Among the other topics included are a study from the Defense and Veterans Brain Injury Center reporting that servicemembers with previous TBIs had more symptoms in the first three months after a subsequent injury, compared with those with their first TBI, and a study from the Naval Health Research Center, which found that servicemembers with mild TBI were more likely to report health symptoms, such as headache, back pain, ringing in the ears, dizziness and memory problems.
1. Bazarian JJ, Donnelly K, Peterson DR, Warner GC, Zhu T, Zhong J. The relation between posttraumatic stress disorder and mild traumatic brain injury acquired during Operations Enduring Freedom and Iraqi freedom. J Head Trauma Rehabil. 2013 Jan;28(1):1-12. doi: 0.1097/HTR.0b013e318256d3d3. PubMed PMID: 22647965.